Protective Immunogenicity of Group A Streptococcal M-related Proteins

Overview

Journal Clin Vaccine Immunol

Publisher American Society for Microbiology

Specialties Allergy & Immunology
Pathology

Date 2015 Jan 30

PMID 25630406

Citations 11

Authors

James B Dale

Shannon E Niedermeyer

Tina Agbaosi

Nicholas D Hysmith

Thomas A Penfound

Claudia M Hohn

Matthew Pullen

Michael I Bright

Daniel S Murrell

Lori E Shenep

Harry S Courtney

Affiliations

Soon will be listed here.

Abstract

Many previous studies have focused on the surface M proteins of group A streptococci (GAS) as virulence determinants and protective antigens. However, the majority of GAS isolates express M-related protein (Mrp) in addition to M protein, and both have been shown to be required for optimal virulence. In the current study, we evaluated the protective immunogenicity of Mrp to determine its potential as a vaccine component that may broaden the coverage of M protein-based vaccines. Sequence analyses of 33 mrp genes indicated that there are three families of structurally related Mrps (MrpI, MrpII, and MrpIII). N-terminal peptides of Mrps were cloned, expressed, and purified from M type 2 (M2) (MrpI), M4 (MrpII), and M49 (MrpIII) GAS. Rabbit antisera against the Mrps reacted at high titers with the homologous Mrp, as determined by enzyme-linked immunosorbent assay, and promoted bactericidal activity against GAS emm types expressing Mrps within the same family. Mice passively immunized with rabbit antisera against MrpII were protected against challenge infections with M28 GAS. Assays for Mrp antibodies in serum samples from 281 pediatric subjects aged 2 to 16 indicated that the Mrp immune response correlated with increasing age of the subjects. Affinity-purified human Mrp antibodies promoted bactericidal activity against a number of GAS representing different emm types that expressed an Mrp within the same family but showed no activity against emm types expressing an Mrp from a different family. Our results indicate that Mrps have semiconserved N-terminal sequences that contain bactericidal epitopes which are immunogenic in humans. These findings may have direct implications for the development of GAS vaccines.

Citing Articles

Serum Immune Responses to Group A Streptococcal Antigens following Pharyngeal Acquisitions among Children in Cape Town, South Africa.

Salie M, Muhamed B, Engel K, Rampersadh K, Daniels R, Mhlanti L mSphere. 2023; 8(3):e0011323.

PMID: 37154726 PMC: 10286702. DOI: 10.1128/msphere.00113-23.

Correlates of immunity to Group A Streptococcus: a pathway to vaccine development.

Frost H, Excler J, Sriskandan S, Fulurija A NPJ Vaccines. 2023; 8(1):1.

PMID: 36650164 PMC: 9844947. DOI: 10.1038/s41541-022-00593-8.

Utility of Human Immune Responses to GAS Antigens as a Diagnostic Indicator for ARF: A Systematic Review.

Salie M, Rampersadh K, Muhamed B, Engel K, Zuhlke L, Dale J Front Cardiovasc Med. 2021; 8:691646.

PMID: 34355030 PMC: 8329041. DOI: 10.3389/fcvm.2021.691646.

Nonimmune antibody interactions of Group A Streptococcus M and M-like proteins.

Mills J, Ghosh P PLoS Pathog. 2021; 17(2):e1009248.

PMID: 33630944 PMC: 7906336. DOI: 10.1371/journal.ppat.1009248.

Analysis of Global Collection of Group A Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins.

Frost H, Davies M, Delforge V, Lakhloufi D, Sanderson-Smith M, Srinivasan V mSphere. 2020; 5(1).

PMID: 31915226 PMC: 6952200. DOI: 10.1128/mSphere.00806-19.

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